May 2005
The food you eat is broken down into glucose. Mitochondria use oxygen to turn glucose into energy. If there is not enough oxygen or if the mitochondria aren't working properly, cells must make energy in a different way. Making energy without oxygen produces lactic acid as a byproduct.
Lactic acid is quickly converted to lactate in the blood. Though lactic acid and lactate are not the same, the terms are often used interchangeably. Lactate is formed when lactic acid loses a hydrogen atom. The hydrogen atom lost by lactic acid stays in the blood; this decreases the blood's pH and makes it more acidic.
Your muscles produce lactic acid and lactate when you exercise. It is the lactate in your muscles that makes them feel sore after a workout. Lactate is broken down by your liver. If your body produces too much lactate, your liver may have a hard time keeping up.
Nucleoside reverse transcriptase inhibitors (NRTIs) can cause hyperlactatemia by disrupting the function of the mitochondria. This is known as mitochondrial toxicity. NRTIs block the function of polymerase- gamma, a protein that mitochondria need to do their job properly. When the mitochondria don't work efficiently, excess lactate is produced.
NRTIs can also cause the liver to become fatty, a condition called hepatic steatosis (see Hepatotoxicity Fact Sheet). A fatty liver doesn't work well and can't break down lactate efficiently.
Severe hyperlactatemia leads to lactic acidosis. Lactic acidosis is a serious but very rare complication of treatment with NRTIs. Although all NRTIs are associated with hyperlactatemia and lactic acidosis, people taking Zerit (stavudine) and Videx (didanosine) seem to be at greater risk than people taking other NRTIs.
Signs and symptoms of severe hyperlactatemia and lactic acidosis are:
Your doctor should also perform a physical exam to check for an enlarged liver and may order a CT scan or ultrasound of your liver.
Lactate levels may vary depending on how the test was performed and which lab did the testing. Your doctor can help you understand what your lactate level means.
You should not stop taking any anti-HIV medications without talking to your doctor, even if you have symptoms of lactic acidosis. If you are diagnosed with lactic acidosis, you and your doctor will decide how to stop your anti-HIV medications, when to restart medications, and which ones to take when you go back to treatment.
If you have only mild hyperlactatemia and no symptoms, you may not need to change your HIV treatment regimen. At this time, there is no evidence that people with mild hyperlactatemia are at increased risk for lactic acidosis.
Terms Used in This Fact SheetLiver function tests (LFTs): tests that measure the blood levels of liver enzymes (proteins made and used by the liver) to determine if your liver is working properly. Mitochondrial toxicity: also referred to as mitochondrial dysfunction. Damage to the mitochondria that can cause problems in the heart, nerves, muscles, pancreas, kidneys, and liver. It may also cause changes in the blood, such as thrombocytopenia (too few platelets), anemia (too few red blood cells), and neutropenia (too few neutrophils). Mitochondrial damage can lead to lactic acidosis and hepatic steatosis (fatty liver) and may also play a role in lipodystrophy (see Lipodystrophy Fact Sheet). Nucleoside reverse transcriptase inhibitor (NRTI): class of anti-HIV medication. NRTIs are faulty versions of the building blocks (nucleosides) used by reverse transcriptase, a protein that HIV needs to make copies of itself. The NRTIs approved by the FDA are Combivir, Emtriva, Epivir, Epzicom, Hivid, Retrovir, Trizivir, Truvada, Videx, Viread, Zerit, and Ziagen. |
This information is based on the U.S. Department of Health and Human Services' Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents (available at http://aidsinfo.nih.gov).